During in vitro fertilization cycles, human chorionic gonadotropin (hCG) is given to initiate periovulatory events in place of the coincident surges of follicle stimulating hormone (FSH) and luteinizing hormone (LH) that normally occur at midcycle. The efficacy of FSH as an alternative periovulatory stimulus in primates is unknown. In this study, oocyte nuclear maturation, granulosa cell luteinization and corpus luteum function following recombinant (r)-FSH was compared to r-hCG. Rhesus monkeys (n=5/group) received r-hFSH (Serono) with GnRH antagonist (Antide; Serono) to stimulate multiple follicular growth followed by a bolus of r-hCG (Serono, 1000 IU) or r-hFSH (Serono; 2500 IU). Bioactive hCG achieved peak levels (1360 q 208 ng/ml) between 2-8 hr after r-hCG injection and remained at surge (r100 ng/ml) levels for >48 hr. Immunoreactive FSH decreased from 13 q 1 mIU/ml to 0.5 mIU/ml by 96 hr post-hCG. Immunoreactive FSH rose from baseline (11 q 1 mIU/ml) to peak levels (1455 q 314) 2-8 hr after r-hFSH, and declined to pretreatment levels by 96 hr. Bioactive LH levels were <3 ng/ml following r-hFSH injection. The proportion of oocytes resuming meiosis to metaphase I + metaphase II and fertilizing in vitro were comparable between r-hCG (88%; 50 q 17%) and r-hFSH (97%; 47 q 19%), respectively. In vitro progesterone (P) production and immunocytochemical staining for P receptor in granulosa cells were similar between groups. While peak levels of serum P on day 4 of the luteal phase were comparable between groups, levels were higher (P<0.05) from days 6-9 in r-hCG relative to r-hFSH. Thus, a bolus of r-hFSH was equivalent to r-hCG for the reinitiation of oocyte meiosis and oocyte fertilization plus granulosa cell luteinization in gonadotropin-stimulated macaques. The data are consistent with rodent models wherein FSH can substitute for LH/CG to initiate early periovulatory events, but a midcycle FSH surge is inadequate to sustain normal luteal function in primates.